Brian MacVicar, PhD

Significant Contributions

Two-photon laser scanning microscopy to show that astrocyte calcium signals cause constrictions of cerebral blood vessels- 2004-2008.  We used two-photon laser scanning microscopy and uncaging of calcium to show unequivocally that calcium transients in identified astrocytes cause vascular constrictions thereby regulating cerebral blood flow (Mulligan & MacVicar 2004 Nature 431:195). In Gordon et al, 2008 Nature we continued this work by showing that astrocytes regulate both dilation and constriction of adjacent arterioles via a complex response to metabolic changes. This provides new insight into how the brain intrinsically regulates its own blood supply and into the pathological changes in cbf observed following stroke, SAH and vascular dementias.

Hemichannel opening contributes to neuron death in ischemia and Electrotonic coupling in Neurons-   We reported in 2 Science papers recently that ischemia (Thompson et al 2006) and NMDA receptor activation (Thompson et al, 2008) triggers the opening of gap junction hemichannels in neurons.  This surprising discovery that helps explain the ionic dysregulation that leads to necrosis in stroke and the generation of seizure discharges from NMDA receptor stimulation. As a graduate student (1976 to 1980) I discovered for the first time that neurons in the hippocampus are electrotonically coupled.  This was the first direct demonstration of electrotonic coupling in the mammalian CNS.  The evidence was obtained using simultaneous dual intracellular recordings from neurons in hippocampal brain slices (MacVicar and Dudek, 1981, Science 213: 782).  The recent pannexin discoveries provide a mechanistic link to my graduate work.

Astrocyte Ion Channels- 1983-1987: During the first few years as a faculty member at the University of Calgary, I developed a research program to analyze the properties of astrocytes with a view to showing that these cells are not passive cells.  I showed for the first time that astrocytes have voltage-gated calcium channels (MacVicar, 1984, Science 226: 1345).  This discovery started a field of research analyzing the active membrane properties of glial cells. We analyzed the calcium signaling properties of astrocytes in intact brain tissue to determine how astrocyte calcium responses might influence neurons.  We simultaneously mapped spreading depression and intracellular calcium to determine the relationship between calcium waves in astrocytes and spreading depression (Basarsky et al., 1998, J Neurosci 18:7189).  We have discovered a novel mechanism of glutamate release in brain slices that involved release from volume activated chloride channels (Basarsky et al., 1999, J Neurosci 19:6439; Crepel, 1998, J Neurosci18:1196).

Imaging Intrinsic Optical Signals- 1990 to present: My lab developed imaging techniques to monitor intrinsic optical signals in brain tissue and we were the first to image synaptic activation in brain slices and in the isolated whole brain preparation (MacVicar et al., 1991 J Neurosci 11: 1458; Federico et al., 1994 Neuroscience 58:461) and in human during operations (MacVicar et al.  Optical Imaging System for Neurosurgery. U.S. Patent #5,215,095).  In the course of these experiments we developed software for imaging experiments.  This software was licensed to Axon Instruments (Axon Imaging Workbench) for world-wide distribution and is now sold to INDEC. I was the first to describe using infrared video imaging to observe cells in brain slices.  This technique is widely used to visualize neurons in brain slices for patch recordings (MacVicar, 1984, J Neurosci. Meth. 12: 133).